A human colon cancer cell capable of initiating tumour growth in immunodeficient mice

Colon cancer is one of the best-understood neoplasms from a genetic perspective, yet it remains the second most common cause of cancer-related death, indicating that some of its cancer cells are not eradicated by current therapies. What has yet to be established is whether every colon cancer cell possesses the potential to initiate and sustain tumour growth, or whether the tumour is hierarchically organized so that only a subset of cells--cancer stem cells--possess such potential. Here we use renal capsule transplantation in immunodeficient NOD/SCID mice to identify a human colon cancer-initiating cell (CC-IC). Purification experiments established that all CC-ICs were CD133+; the CD133- cells that comprised the majority of the tumour were unable to initiate tumour growth. We calculated by limiting dilution analysis that there was one CC-IC in 5.7 x 10(4) unfractionated tumour cells, whereas there was one CC-IC in 262 CD133+ cells, representing >200-fold enrichment. CC-ICs within the CD133+ population were able to maintain themselves as well as differentiate and re-establish tumour heterogeneity upon serial transplantation. The identification of colon cancer stem cells that are distinct from the bulk tumour cells provides strong support for the hierarchical organization of human colon cancer, and their existence suggests that for therapeutic strategies to be effective, they must target the cancer stem cells.     

Inducing apoptosis of cancer cell and inhibiting mice’s malignant tumour growth by magnetic fields

It was found that the growth of malignant tumour in mice was inhibited and the ability of immune cell’s dissolving cancer cells was enhanced by ultralow frequency (ULF) pulsed gradient magnetic field. The DNA contents of nuclei decreased which indicated that magnetic field can block DNA replication and mitosis of cancer cells. It was observed that magnetic field inhibited the cancer cell’s metabolism, lowered its malignancy, and restrained its rapid and heteromorphic growth. The morphology properties of Programmed Cell Death (PCD) of the cancer cells of the treated group by magnetic field was observed for the first time. The heterochromatin condensed and coagulated together along the nuclear membrane; the endoplasmic reticulums expanded and fused with the cellular membrane; many apoptotic bodies which were packed by the cellular membrane appeared and were devoured by the lymphocytes and plasma. Foundation item: Supported by the National Natural Science Foundation of China Biography: ZHANG Hu-sheng(1938-), male, Professor     

Lack of linkage of familial Wilms' tumour to chromosomal band 11p13

Wilms' tumour (WT), a paediatric renal neoplasm, affect approximately 1 in 10,000 children. One or both kidneys can be affected and 5-10% of tumours are bilateral. Most tumours occur sporadically; however, around 1% of the cases are familial, with siblings or cousins most often being affected. Familial cases are more frequently bilateral, and familial and bilateral tumours are diagnosed at an earlier age. On the basis of these observations, it was proposed that the development of WT requires two mutations. In most sporadic unilateral WT, both are somatic; in familial and bilateral tumours the first is thought to be germinal. Cytogenetic and molecular studies have demonstrated germinal mutations in WT/aniridia patients and somatic mutations in sporadic WT at chromosomal band 11p13. To investigate whether familial predisposition to WT is due to a germinal 11p13 mutation, we studied a WT family with seen DNA markers that span the 11p13 region. We found that familial WT predisposition was not genetically linked to any of the 11p13 markers. This suggests that the gene involved in familial WT predisposition is outside 11p13 and is distinct from the gene involved in tumorigensis and in WT predisposition in WT/aniridia 11p13-deletion patients.     

Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice.

T cells that recognize self antigen are clonally deleted in the thymus--a maturation process that occurs in the context of histocompatibility molecules and the T-cell receptor. The minor lymphocyte stimulation antigens (Mls) effect these deletions through interactions with the V beta portion of the T-cell receptor, thus mimicking bacterial 'superantigens'. Intrigued by the fact that each known Mls gene maps to the same chromosomal region as an endogenous mouse mammary tumour virus (Mtv), we reevaluated the linkage relationships between the two gene families. Here we report perfect concordance in inbred and recombinant inbred mice between the presence of four Mtv proviruses with the expression of Mls gene products. These data suggest a general model in which mammary tumour virus gene products themselves are the ligands that shape a considerable portion of the immunological repertoire of common laboratory mice.     

一种新的呫诺美林衍生物促进小鼠神经元生成

0 引言 毒蕈碱乙酰胆碱受体(M受体)是动物体内重要的神经递质受体,在中枢神经系统主要表达M1受体.M1受体与动物的认知功能及阿尔茨海默病(AD)的神经退行性病理过程密切相关.研究表明,许多M1受体激动剂能通过激活M1受体,缓解AD病理症状,并改善AD病人的认知能力,因此可以作为潜在的AD治疗药物[1].     

Suppression of a myosin defect by a kinesin-related gene.

Motor proteins in cells include myosin, which is actin-based, and kinesin, dynein and dynamin, which are microtubule-based. Several proteins have recently been identified that have amino-acid sequences with similarity to the motor domains of either myosin or kinesin, but are otherwise dissimilar. This has led to the suggestion that these may all be motor proteins, but that they are specialized for moving different cargos. Genetic analysis can address the question of the different functions of these new proteins. Studies of a temperature-sensitive mutation (myo2-66) in a gene of the myosin superfamily (MYO2) have implicated the Myo2 protein (Myo2p) in the process of polarized secretion in yeast (Saccharomyces cerevisiae). To understand more about the role of Myo2p, we have looked for 'multicopy suppressors' (heterologous genes that, when overexpressed, can correct the temperature sensitivity of the myo2-66 mutant). Here we report the identification of such a suppressor (SMY1) that (surprisingly) encodes a predicted polypeptide sharing sequence similarity with the motor portion of proteins in the kinesin superfamily.     

Defining the mode of tumour growth by clonal analysis

Recent studies using the isolation of a subpopulation of tumour cells followed by their transplantation into immunodeficient mice provide evidence that certain tumours, including squamous skin tumours, contain cells with high clonogenic potential that have been referred to as cancer stem cells (CSCs). Until now, CSC properties have only been investigated by transplantation assays, and their existence in unperturbed tumour growth is unproven. Here we make use of clonal analysis of squamous skin tumours using genetic lineage tracing to unravel the mode of tumour growth in vivo in its native environment. To this end, we used a genetic labelling strategy that allows individual tumour cells to be marked and traced over time at different stages of tumour progression. Surprisingly, we found that the majority of labelled tumour cells in benign papilloma have only limited proliferative potential, whereas a fraction has the capacity to persist long term, giving rise to progeny that occupy a significant part of the tumour. As well as confirming the presence of two distinct proliferative cell compartments within the papilloma, mirroring the composition, hierarchy and fate behaviour of normal tissue, quantitative analysis of clonal fate data indicates that the more persistent population has stem-cell-like characteristics and cycles twice per day, whereas the second represents a slower cycling transient population that gives rise to terminally differentiated tumour cells. Such behaviour is shown to be consistent with double-labelling experiments and detailed clonal fate characteristics. By contrast, measurements of clone size and proliferative potential in invasive squamous cell carcinoma show a different pattern of behaviour, consistent with geometric expansion of a single CSC population with limited potential for terminal differentiation. This study presents the first experimental evidence for the existence of CSCs during unperturbed solid tumour growth.